title: Efficacy and safety of recombinant factor XIII on reducing blood transfusions in cardiac surgery: a randomized, placebo-controlled, multicenter clinical trial.
abstract: OBJECTIVE
  Cardiac surgery with cardiopulmonary bypass frequently leads to excessive bleeding, obligating blood product transfusions. Because low factor XIII (FXIII) levels have been associated with bleeding after cardiac surgery, we investigated whether administering recombinant FXIII after cardiopulmonary bypass would reduce transfusions.
  
  
  METHODS
  In this double-blinded, placebo-controlled, multicenter trial, 409 cardiac surgical patients at moderate risk for transfusion were randomized to receive an intravenous dose of recombinant FXIII, 17.5 IU/kg (n = 143), 35 IU/kg (n = 138), or placebo (n = 128) after cardiopulmonary bypass. Transfusion guidelines were standardized. The primary efficacy outcome was avoidance of allogeneic blood products for 7 days postsurgery. Secondary outcomes included amount of blood products transfused and reoperation rate. Serious adverse events were measured for 7 weeks.
  
  
  RESULTS
  Study groups had comparable baseline characteristics and an approximately 40% decrease in FXIII levels after cardiopulmonary bypass. Thirty minutes postdose, FXIII levels were restored to higher than the lower 2.5th percentile of preoperative activity in 49% of the placebo group, and 85% and 95% of the 17.5- and 35-IU/kg recombinant FXIII groups, respectively (P < .05 for both treatments vs placebo). Transfusion avoidance rates were 64.8%, 64.3%, and 65.9% with placebo, 17.5 IU/kg, and 35 IU/kg recombinant FXIII (respective odds ratios against placebo, 1.05 [95% confidence interval, 0.61-1.80] and 0.99 [95% confidence interval, 0.57-1.72]). Groups had comparable adverse event rates.
  
  
  CONCLUSIONS
  Replenishment of FXIII levels after cardiopulmonary bypass had no effect on transfusion avoidance, transfusion requirements, or reoperation in moderate-risk cardiac surgery patients (ClinicalTrials.gov identifier: NCT00914589).
authors.affiliation: Department of Anesthesia and the Toronto General Research Institute, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada. Electronic address: keyvan.karkouti@uhn.ca.
authors.forename: Keyvan
authors.initials: K
authors.lastname: Karkouti
authors.forename: Christian
authors.initials: C
authors.lastname: von Heymann
authors.forename: Christian M
authors.initials: CM
authors.lastname: Jespersen
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Korte
authors.forename: Jerrold H
authors.initials: JH
authors.lastname: Levy
authors.forename: Marco
authors.initials: M
authors.lastname: Ranucci
authors.forename: Frank W
authors.initials: FW
authors.lastname: Sellke
authors.forename: Howard K
authors.initials: HK
authors.lastname: Song
mesh_terms: D000368:Aged; D001803:Blood Transfusion; D002170:Canada; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D003029:Coagulants / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005060:Europe; D005176:Factor XIII / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007557:Israel; D007564:Japan; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D019106:Postoperative Hemorrhage / Q000209:etiology / Q000517:prevention & control*; D011300:Preoperative Care; D011994:Recombinant Proteins / Q000008:administration & dosage; D012086:Reoperation; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: D003029:Coagulants; D011994:Recombinant Proteins; D005176:Factor XIII
keywords: 37; AE; CPB; FXIII; adverse event; cardiopulmonary bypass; factor XIII